Studies are proposed to elucidate the mechanism of thyroid hormone action in the heart. To determine whether thyroid hormone induced changes in cardiac protein synthesis are mediated through alterations in mRNA levels we will quantitate mRNA concentration, protein concentration and fractional protein turnover in different thyroid states. Thyroid hormone induced changes in mRNA concentration will be further evaluated by an analysis of the composition of cardiac mRNA by sequence complexity analysis. These studies will reveal if thyroid hormone induced increases in cardiac mRNA concentration are due to a general increase in mRNA of the same coding capacity as present in hypothyroid animals, represents the formation of additional mRNA species with different coding capacity or a combination of these factors. In addition, the influence of thyroid hormone on the formation of the mRNA coding for myosin heavy chain polypeptide and on the level of the myosin heavy chain polypeptide itself will be determined. The binding capacity of cardiac nuclear T3 receptors will be determined in starved, hepatectomized, diabetic animals and in rats after glucagon administration. If changes in binding capacity occur, the physiological consequences of this change will be evaluated by determining the thyroid hormone response of certain cardiac enzymes.